Oxytocin Facilitates Approach Behavior to Positive Social Stimuli via Decreasing Anterior Insula Activity

Background: The neuropeptide oxytocin can extensively modulate human social behavior and affective processing, and its effects can be interpreted in terms of mediating approach-avoidance motivational processes. However, little is known about how oxytocin mediates approach-avoidance behavior and particularly the underlying neural mechanisms. Methods: In a randomized, double-blind, between-subject design, the present pharmaco-fMRI study used an approach-avoidance paradigm to investigate oxytocin's effects on approach-avoidance behavior and associated neural mechanisms. Results: Results revealed that oxytocin generally decreased activity in the right striatum irrespective of response (approach/avoidance) and social context, suggesting an inhibitory effect on motivational representation during both appetitive approach and aversive avoidance. Importantly, while on the behavioral level oxytocin selectively enhanced accuracy when approaching social positive stimuli, on the neural level it decreased left ventral and right dorsal anterior insula activity in response to social vs nonsocial positive stimuli compared with the placebo treatment. The left ventral anterior insula activity was negatively correlated with the corresponding accuracy difference scores in the oxytocin but not in the placebo group. Conclusion: Given the role of the ventral anterior insula in emotional processing and the dorsal anterior insula in salience processing, the oxytocin-induced suppression of activity in these regions may indicate that oxytocin is acting to reduce interference from hyper-activity in core regions of the emotional and salience networks when approaching salient positive social stimuli and thereby to promote social interaction. Thus, oxytocin may be of potential therapeutic benefit for psychiatric disorders exhibiting avoidance of social stimuli.